In adults, bone is constantly being remodeled, first being broken down (bone resorption) and then being rebuilt (bone formation). The resorption and reformation of bone is important for repair of microfractures and to allow modification of structure in response to stress and other biomechanical forces. Bone formation is normally tightly coupled to bone resorption, so that bone mass does not change. Bone diseases occur when formation and resorption are uncoupled.
Several assays are available that measure bone turnover markers (BTMs). These assays measure collagen breakdown products and other molecules released from osteoclasts and osteoblasts during the process of bone resorption and formation. Markers that are specific to bone formation include bone-specific alkaline phosphatase (BALP), osteocalcin, and N-terminal propeptide of type 1 procollagen (P1NP); markers specific to bone resorption include N-telopeptide of type 1 collagen (NTX), C-terminal telopeptide of type 1 collagen (CTX), and pyridinoline cross-links (table 1).
The use of BTMs in clinical trials has been helpful in understanding the mechanism of action of therapeutic agents. However, their role in the care of individual patients is not well established. Biologic and laboratory variability in BTM values has confounded their widespread use in clinical practice (table 2). BTMs give some indication about the future risk for bone loss and fractures. More importantly, they are useful in monitoring the efficacy of antiresorptive therapy in populations of patients with osteoporosis.
This topic will review the clinical use of biochemical BTMs. The physiology of BTMs, their relationship to the process of bone remodelling, and their use in other bone disorders are reviewed separately. (See "Bone physiology and biochemical markers of bone turnover" and "Osteoporosis in patients with chronic kidney disease: Diagnosis, evaluation, and management", section on 'Biochemical markers of bone turnover' and "Investigational biologic markers in the diagnosis and assessment of rheumatoid arthritis", section on 'Bone-specific markers' and "Clinical manifestations and diagnosis of Paget disease of bone", section on 'Role of biochemical studies'.)
The measurement of bone turnover markers (BTMs) is complicated by large random within-patient variability, biologic variability (age, gender, body mass index [BMI], circadian, and menstrual variation), and poor standardization of most assays (table 2) [1,2]. These issues have confounded their widespread use in clinical practice. However, some clinical assays are now automated. In 2012, The National Bone Health Alliance (NBHA) initiated a project to standardize BTM sample collection procedures in the United States and to establish a reference range of serum N-terminal propeptide of type 1 procollagen (P1NP, bone formation) and serum C-terminal telopeptide of type 1 collagen (CTX, bone resorption), the markers that they, the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), identified as most promising for clinical use [3,4]. This project is ongoing.